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Table of Contents    
BRIEF REPORT
Year : 2012  |  Volume : 60  |  Issue : 1  |  Page : 82-85

Analysis of the genotype of diacylglycerol kinase delta single-nucleotide polymorphisms in Parkinson disease in the Han Chinese population


1 Department of Neurology, West China Hospital, SiChuan University, Chengdu Sichuan, China
2 Department of Medical Genetics, West China Hospital, SiChuan University, Chengdu Sichuan, China

Date of Submission30-Oct-2011
Date of Decision21-Nov-2011
Date of Acceptance01-Jan-2012
Date of Web Publication7-Mar-2012

Correspondence Address:
Hui-Fang Shang
Department of Neurology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.93607

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 » Abstract 

Numerous Single-Nucleotide Polymorphisms (SNPs) of the Diacylglycerol Kinase Delta (DGKD) isoform 1 gene have been associated with Parkinson Disease (PD) in the genome-wide association studies of Caucasian population. This association has not been proven in the Han Chinese PD patients. This study included 376 unrelated Han Chinese PD patients from West China and 273 unrelated healthy controls from the same region. Five SNPs (rs2971859, rs1550532, rs2305539, rs2034762, and rs2242102) were genotyped using the Sequenom iPLEX Assay technology. No significant differences were observed in genotype frequencies and in the Minor Allele Frequency (MAF) in the five SNPs between PD patients and controls, early-onset PD and controls, late-onset PD and controls, and between early-onset and late-onset PD patients. The present study is the first to report on the lack of association of DGKD SNPs with PD in the Han Chinese population. More related studies involving larger numbers of participants are necessary to confirm the present finding.


Keywords: Diacylglycerol Kinase Delta gene, Parkinson disease, polymorphism


How to cite this article:
Song W, Chen YP, Huang R, Chen K, Pan PL, Li J, Yang Y, Shang HF. Analysis of the genotype of diacylglycerol kinase delta single-nucleotide polymorphisms in Parkinson disease in the Han Chinese population. Neurol India 2012;60:82-5

How to cite this URL:
Song W, Chen YP, Huang R, Chen K, Pan PL, Li J, Yang Y, Shang HF. Analysis of the genotype of diacylglycerol kinase delta single-nucleotide polymorphisms in Parkinson disease in the Han Chinese population. Neurol India [serial online] 2012 [cited 2019 Oct 23];60:82-5. Available from: http://www.neurologyindia.com/text.asp?2012/60/1/82/93607



 » Introduction Top


Parkinson Disease (PD), the second most common neurodegenerative disorder, is characterized by several main cardinal symptoms such as tremor, rigidity, bradykinesia, and postural instability. [1] The etiology of this disease remains unclear. A number of genes including SNCA (α-synuclein, PARK1), Parkin (PARK2), UCHL-1 (PARK5), PINK1 (PTEN1-induced putative kinase, PARK6), DJ-1 (PARK7), LRRK2 (PARK8), ATP13A2 (PARK9), and Omi/HtrA2 (PARK13) have been identified as causative genes for familial PD,[2],[3] and several PARK loci without candidate genes have been linked with familial PD. [4],[5] Multiple genetic and environmental factors are considered to contribute to the development of PD. [2]

The Diacylglycerol Kinase Delta (DGKD) isoform 1 gene is located at 2q37.1 and encodes a 130-kD protein known as DGKD, which functions as a cytoplasmic enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. [6] Several recent case-control Genome-Wide Association Studies (GWAS) on the associations among numerous Single Nucleotide Polymorphisms (SNPs) of the DGKD gene and PD in the Caucasian population have yielded inconsistent findings. [7],[8],[9] No data on the association of Asian PD patients with DGKD gene SNPs are available. Ethnicity plays an important role in genetic analysis. Hence, a large case-control study that included 649 Han individuals from mainland China was performed to clarify the association between DGKD SNPs (rs2971859, rs1550532, rs2305539, rs2034762, and rs2242102) (selected from the website http://www.pdgene.org/) and Asian PD patients.


 » Materials and Methods Top


Subjects

A total of 376 sporadic Han PD patients from the Department of Neurology of West China Hospital, Sichuan University, from June 2007 to April 2011, were included in the study. Patients were diagnosed according to the UK PD Society Brain Bank Clinical Diagnostic Criteria for PD. [10] Sporadic PD was defined as PD without a family history of the disease. For comparison, 273 Han healthy controls matched by gender, age, and area of residence were included in the control group. All controls subjects were examined by a neurologist to exclude neurological disorders. A written informed consent was obtained from patients and controls. Peripheral blood samples were collected from all patients and controls. Genomic DNA was collected from the peripheral blood leukocytes by standard phenol/chloroform procedures. [11] The present study was approved by the Ethics Committee of Sichuan University.

Genetic and statistical analyses

The Sequenom iPLEX Assay technology (Sequenom iPLEX Assay, San Diego) was used on all patients and controls genotyped for SNPs according to the manufacturer's instructions. The Minor Allele Frequency (MAF) and Odds Ratio (OR) with a 95% Confidence Interval (CI) were reported for each SNP. Fisher's exact test was performed to check the Hardy-Weinberg Equilibrium (HWE), genotype frequency, and MAF of each selected SNP for the PD patients and the controls. The ORs were adjusted by age and gender to minimize their effect. The Bonferroni method was used to adjust the significance level. All analyses were conducted using the SPSS11.0 software (SPSS, Inc, Chicago, IL, USA).


 » Results Top


Clinical data and genetic finding

All included patients presented with disease progression such as rigidity, bradykinesia, resting tremor, and good response to levodopa. The mean age of onset for PD patients was 56.39±11.78 year, not significantly different from the mean age of the control group, 54.5±11.73 year (P=0.3). The mean disease duration of patients was 4.46±4.04 year. Approximately 271 patients (late-onset group) were older than 50 year, whereas 105 patients (early-onset group) were younger than 50 year. The allele and genotype distributions for the five SNPs in the PD patients and controls did not deviate significantly from the HWE. After the Bonferroni adjustment, no significant differences were found in the genotype frequencies and the MAF for the five SNPs between the PD patients and the controls [Table 1], between the early-onset PD and controls [Table 2], between the late-onset PD and controls [Table 2], and between the early-onset and late-onset PD [Table 3].
Table 1: Analysis the genotype distribution and the MAF of each SNP between PD patients and controls

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Table 2: Analysis the genotype distribution and the MAF of each SNP between the PD patients and the controls according to age of onset (50 years)

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Table 3: Analysis of the genotype and MAF between the early-onset and late-onset PD

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 » Discussion Top


To the best of our knowledge, this is the first reported lack of association of DGKD gene SNPs in PD patients of Han Chinese origin. Recent expression studies in Drosophila and mouse have reported that DGKD is involved in the development and function of the central nervous system. [12] The ubiquitination of the Epidermal Growth Factor Receptor (EGFR) was enhanced in the DGKD-deficient cells, which attenuated the steady-state levels of EGFR and promoted its ligand-induced degradation. [13] These effects may be caused by reduced expression of the de-ubiquitinase-Ubiquitin-Specific Protease 8 (USP8). [13] The DGKD gene location is close to the location of the GIGY12 gene, which has been designed as Park11, suggesting the role of DGKD in the development of PD. However, the negative finding of the present study was consistent with the results of most studies, [7],[8],[9] indicating that DGKD gene SNPs do not play an important role in Han Chinese PD patients. The inconsistent findings among different studies were probably influenced by various factors such as sample size and ethnicity. Thus, further studies are needed using GWAS-linked data, especially research on the ethnic-specific effect of common variants. More related studies with larger numbers of participants are necessary to confirm the present findings.


 » Acknowledgments Top


The authors are thankful to the patients for their participation in the study. This study was supported by the National Science Fund of China (Grant no.30973149) and Science and Technology Bureau Fund of SiChuan Province (No.2010SZ0069).

 
 » References Top

1.Fahn S. Description of Parkinson's disease as a clinical syndrome. Ann N Y Acad Sci 2003;991:1-14.  Back to cited text no. 1
    
2.Schapira AH, Jenner P. Etiology and pathogenesis of Parkinson's disease. Mov Disord 2011;26:1049-55.  Back to cited text no. 2
    
3.Bekris LM, Mata IF, Zabetian CP. The Genetics of Parkinson Disease. J Geriatr Psychiatry Neurol 2010;23:228-42.  Back to cited text no. 3
    
4.West AB, Zimprich A, Lockhart PJ, Farrer M, Singleton A, Holtom B, et al. Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes. Europ J Hum Genet 2001;9:659-66.  Back to cited text no. 4
    
5.Farrer MJ, Haugarvoll K, Ross OA, Stone JT, Milkovic NM, Cobb SA, et al. Genomewide association, Parkinson disease, and PARK10. Am J Hum Genet 2006;78:1084-8.  Back to cited text no. 5
    
6.Harada BT, Knight MJ, Imai S, Qiao F, Ramachander R, Sawaya MR, et al. Regulation of enzyme localization by polymerization: polymer formation by the SAM domain of diacylglycerol kinase delta1. Structure 2008;16:380-7.  Back to cited text no. 6
    
7.Fung HC, Scholz S, Matarin M, Simón-Sánchez J, Hernandez D, Britton A, et al. Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data. Lancet Neurol 2006;5:911-6.  Back to cited text no. 7
    
8.Pankratz N, Wilk JB, Latourelle JC, DeStefano AL, Halter C, Pugh EW, et al. Genomewide association study for susceptibility genes contributing to familial Parkinson disease. Human Genetics 2009;124:593-605.  Back to cited text no. 8
    
9.Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, et al. Genome-Wide Association Study reveals genetic risk underlying Parkinson's disease. Nat Genet 2009;41:1308-12.  Back to cited text no. 9
    
10.Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181-4.  Back to cited text no. 10
    
11.Zhang SS, Fang DF, Hu XH, Burgunder JM, Chen XP, Zhang YW, et al. Clinical feature and DYT1 mutation screening in primary dystonia patients from South-West China. Eur J Neurol 2010;17:846-51.  Back to cited text no. 11
    
12.Leach NT, Sun Y, Michaud S, Zheng Y, Ligon KL, Ligon AH, et al. Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice. Am J Human Genet 2007;80:792-9.  Back to cited text no. 12
    
13.Cai J, Crotty TM, Reichert E, Carraway KLr, Stafforini DM, Topham MK. Diacylglycerol kinase delta and protein kinase C(alpha) modulate epidermal growth factor receptor abundance and degradation through ubiquitin-specific protease 8. J Biol Chem 2010;285:6952-9.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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